The Mitogen-activated Protein (MAP) Kinase Pathway is a key signaling pathway from the cell surface to the nucleus. This signaling cascade controls complex biological processes, such as embryogenesis, differentiation, proliferation, homeostasis and acute hormonal response mechanisms [Endocr. Rev. (2001), 22, 153; Adv. Cancer Res. (1998) 74, 49]. This transduction of information is mediated by the MAP family of kinases that phosphorylate and regulate a wide range of substrates including transcription factors, cytoskeletal elements and other kinases. Intense interest in protein kinases as drug targets has developed over the past few years, the MAP Kinase pathway being of particular focus. For example, inhibitors of B-Raf kinase and MEK have been developed, with the B-Raf inhibitor Sorafenib having been recently commercialized. ERK appears to be a pivotal junction point in the MAP kinase cell-signaling cascade, being the last cytosolic member of the pathway that translocates to the nucleus and instigates the transcription process. Additionally, significant evidence for MAP kinase independent ERK activation pathways in melanoma and other cell lines have been reported [J. Clin. Pathol. (2005), 58, 1163; Oncogene, (1997), 14, 1635; Biochem. Biophys. Research Comm. (2005), 329, 266; Am. J. Physio. Cell. Physiol. 2002, 283, C282; Cell Signal. (2010), 9, 1369], a mechanism by which inactivation of upstream kinase inhibitors may occur. For example, it has been reported that ERK trans-activation pathways are the reasons for the resistance observed during B-Raf kinase targeted melanoma therapy [Br. J. Cancer. (2010), 102, 1724].